Efficacy and Safety of Durvalumab Plus Tremelimumab in Hepatocellular Carcinoma Patients With Portal Vein Thrombosis and High Tumor Burden: A Multicenter Retrospective Analysis.

Aims: This study aimed to evaluate the therapeutic efficacy of durvalumab and tremelimumab (Dur/Tre) in patients with hepatocellular carcinoma (HCC) who had a tumor thrombus in the main portal vein trunk (Vp4) or high tumor burden (HTB).

Methods: A total of 309 patients with BCLC stage B or C HCC who received Dur/Tre between March 2023 and October 2024 were included. HTB was defined as the presence of at least one of the following radiological findings: ≥ 50% liver involvement by HCC, bile duct invasion, or the presence of Vp4.

Optimization of measurements with an ultrasound attenuation coefficient algorithm for quantifying liver fat.

Objectives: Methods for measuring the ultrasound attenuation coefficient (AC) vary across different systems. Some have fixed regions of interest (ROI) while others have movable ROIs. Aims were to evaluate whether, using a system with a fixed ROI, correlation between AC and MRI proton density fat fraction (MRI-PDFF), and performance could be improved by (i) reducing fixed ROI length to 30 mm, changing starting point from the transducer, and (ii) using a movable ROI at different depths.

Carbon-ion radiotherapy achieves outcomes equivalent to surgical resection for hepatocellular carcinoma.

Aim: This study aimed to compare the clinical outcomes of carbon-ion radiotherapy (CIRT) to those of surgical resection (SR) in patients with HCC.

Methods: This retrospective study included 116 and 947 patients initially receiving CIRT and SR in Japanese institutions from September 2010 and June 2022. We used inverse probability of treatment weighting (IPTW) analysis to correct for imbalances in baseline patient characteristics between the 2 groups.

Potential role of Geriatric Nutritional Risk Index as a risk factor for immune-mediated adverse events during durvalumab plus tremelimumab therapy in unresectable hepatocellular carcinoma.

Background: Immune-mediated adverse events (imAEs) are a significant concern in patients with unresectable hepatocellular carcinoma (uHCC) undergoing combination immunotherapy with durvalumab and tremelimumab (Dur/Tre). This study aimed to investigate the potential association of risk factors, particularly nutrition and immune markers, associated with the development of imAEs.

Methods: Between November 2022 and December 2024, 312 patients with uHCC treated with Dur/Tre were enrolled and retrospectively analyzed.

Limited Prognostic Impact of Sustained Virologic Response on Atezolizumab plus Bevacizumab Therapy for HCV-Related Unresectable Hepatocellular Carcinoma.

Aims: Sustained virological response (SVR) is a favorable prognostic factor for patients with hepatocellular carcinoma (HCC) caused by hepatitis C virus (HCV) treated curatively. This study aimed to evaluate the impact of SVR on atezolizumab plus bevacizumab (Atez/Bev) therapy for unresectable HCC (uHCC) caused by HCV.

Methods: A retrospective analysis of 364 uHCC patients treated with Atez/Bev (September 2020-April 2025) and divided into SVR (n = 284) and non-SVR (n = 80) groups was performed, with clinical characteristics, prognosis, and adverse events compared.

Safety and Efficacy of Durvalumab Plus Tremelimumab in Older Individuals With Unresectable Hepatocellular Carcinoma: A Multicenter Analysis.

Aim: To evaluate the safety and efficacy of durvalumab plus tremelimumab (Dur/Tre) in older adults with unresectable hepatocellular carcinoma (HCC).

Methods: A total of 345 patients with HCC who received Dur/Tre were included in this study. Using propensity score matching, we compared outcomes between older (aged ≥ 75 years; n = 120) and younger individuals (n = 120).

Vascular Invasion Within the Resectability Criteria Is a Prognostic Factor in Patients Treated With Atezolizumab and Bevacizumab.

Background And Aims: To assess the outcomes of patients with hepatocellular carcinoma (HCC) who were treated with atezolizumab plus bevacizumab (Atezo/Bev), categorised by oncological resectability criteria, which reflect tumour burden and extent of disease.

Methods: A cohort of 467 HCC patients who received Atezo/Bev was enrolled. Patients were classified into two groups based on oncological resectability criteria: BR (borderline resectable) 1 (n = 153) and BR2 (n = 314).

Identification of high-risk group for diabetes-associated hepatocellular carcinoma using noninvasive test for liver fibrosis.

Background: As diabetes-associated hepatocellular carcinoma (DM-HCC) has surged in Japan, there is an urgent need for effective screening methods. The Fibrosis-4 (FIB-4) index is commonly used for screening, but its age component tends to yield false-positive results in older patients. This study aimed to evaluate the value of the newly developed Fibrosis-3 (FIB-3) index, which excludes age, for identifying high-risk groups for DM-HCC across all age groups.

Clinical Impact of Serum CRP Levels on Advanced HCC Treated With Durvalumab and Tremelimumab: A Multicentre Study.

Aim: This study aimed to evaluate the therapeutic efficacy and prognostic significance of C-reactive protein (CRP) in patients with advanced hepatocellular carcinoma (HCC) receiving durvalumab and tremelimumab (Dur/Tre).

Methods: A total of 167 patients treated with Dur/Tre between March 2023 and March 2024 in Japanese hospitals were included in this retrospective multicentre study. Patients were divided into two groups based on pre-treatment serum CRP levels: the low-CRP group (< 1 mg/dL, n = 106) and the high-CRP group (≥ 1 mg/dL, n = 61).

Neutrophil-Lymphocyte Ratio Predicts Overall Survival in Patients With HCC Treated With Durvalumab Plus Tremelimumab.

Aim: To investigate the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) on outcomes in patients with hepatocellular carcinoma (HCC) treated with durvalumab plus tremelimumab (Dur/Tre).

Methods: A total of 182 patients with HCC who received Dur/Tre were included in the analysis. Univariate and multivariate survival analyses were conducted.

Atezolizumab plus bevacizumab versus Lenvatinib for patients with Barcelona clinic liver cancer stage B (BCLC-B) hepatocellular carcinoma (HCC): A real-world population.

Background: The aim of the present study was to perform a real-world analysis on a large patient cohort with Barcelona Clinic Liver Cancer stage B (BCLC-B) hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (A + B) or with Lenvatinib.

Methods: The study population included patients affected with Barcelona Clinic Liver Cancer stage B (BCLC-B) hepatocellular carcinoma not suitable for locoregional therapies (LRTs) from eastern and western populations, who received atezolizumab plus bevacizumab (A + B) or Lenvatinib as first-line treatment. Univariate and multivariate analyses were used to evaluate predictive factors for overall survival (OS) and time to progression (TTP) while prognostic factors were analyzed by univariate and multivariate analysis using Cox regression model.

Utility of the fibrosis-3 index for predicting liver fibrosis 5 years after achieving sustained virological response in patients with chronic hepatitis C.

Aim: Non-invasive tests for liver fibrosis frequently use serum aminotransferases; however, their accuracy may be influenced by hepatitis virus eradication. This study evaluated the effectiveness of the age-independent FIB-3 index in patients with chronic hepatitis C who achieved sustained virological response (SVR).

Methods: A total of 115 patients who achieved SVR following interferon therapy were analyzed.

Comparison of Surgical Resection and Radiofrequency Ablation for Early-Stage HCC Patients With Child-Pugh Class B.

Aim: The aim of this study is to compare the clinical outcomes of surgical resection (SR) and radiofrequency ablation (RFA) in patients with early-stage hepatocellular carcinoma (HCC) and Child-Pugh Class B liver function.

Methods: Among 7210 treatment-naïve HCC patients in our group between 2000 and 2021, this retrospective study included 41 and 456 patients who underwent SR and RFA, respectively. All included patients had Child-Pugh Class B liver function, an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2, and early-stage HCC (≤ 3 nodules, ≤ 3 cm in diameter).

Prognostic Significance of the BALAD Serological Model in Systemic Therapies for Hepatocellular Carcinoma: A Personalized Approach to the Prediction of Survival Benefit.

Purpose: The BALAD model, a scoring system for staging hepatocellular carcinoma (HCC), is based on five serum markers: bilirubin, albumin, agglutinin-reactive alpha-fetoprotein [AFP], AFP, and des-gamma-carboxy prothrombin. It has shown good ability to predict survival in patients with HCC irrespective of stage and treatment, a high BALAD value being associated with a poor prognosis. However, its prognostic significance is unclear in patients with advanced unresectable HCC (uHCC) who undergo systemic therapies.

Validation of a B-mode ultrasonography scoring system for assessing liver steatosis: A comparison with MRI-Derived proton density fat fraction.

Aim: Noninvasive detection of liver steatosis and monitoring its progression are essential for effective therapeutic management. We validated the diagnostic performance of an ultrasonography (US)-based steatotic liver scoring system, derived from the B-mode method and the hepatic steatosis index (HSI) for the detection of liver steatosis, as identified by proton density fat fraction (PDFF) measurements on magnetic resonance imaging (MRI).

Methods: A total of 916 patients with chronic liver disease were included in the analysis.

Association of liver fibrosis progression with non-liver-related mortality in metabolic dysfunction-associated steatotic liver disease.

Aim: In patients with metabolic dysfunction-associated steatotic liver disease (MASLD), the prognosis and outcomes, particularly non-liver-related mortality, remain insufficiently elucidated. We investigated all-cause mortality in patients with MASLD to elucidate the association of the severity of liver fibrosis with liver-related and non-liver-related mortality in MASLD.

Methods: Among 4528 participants with MASLD, we examined the causes of death and analyzed liver-related and non-liver-related mortality, stratified by the degree of fibrosis using the competing risk method.

Impact of time-of-day atezolizumab plus bevacizumab combination therapy infusion for unresectable hepatocellular carcinoma: A retrospective multicenter study.

Aim: This study aimed to evaluate the impact of infusion timing of time-of-day on clinical outcomes in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab combination therapy.

Methods: A retrospective analysis was conducted using data from 751 unresectable HCC patients treated with atezolizumab plus bevacizumab between September 2020 and April 2024. Patients were categorized into morning (AM; n = 351) and afternoon (PM; n = 400) groups based on infusion timing of time-of-day.

Cachexia Index as a Prognostic Indicator in Patients with Unresectable Hepatocellular Carcinoma Receiving Atezolizumab and Bevacizumab Therapy.

Introduction: We investigated the association between the pretreatment cachexia index (CXI) and survival outcomes in patients with unresectable hepatocellular carcinoma (u-HCC) receiving atezolizumab plus bevacizumab (Atez/Bev).

Methods: We conducted a retrospective analysis of 195 patients with u-HCC treated with Atez/Bev from September 2020 to December 2023. The skeletal muscle mass index (SMI) was calculated by normalizing the psoas muscle area by the square of the height (cm2/m2).

Proposal of discontinuation criteria of atezolizumab plus bevacizumab after curative conversion therapy for unresectable early-to-intermediate-stage hepatocellular carcinoma: a multicenter proof-of-concept study.

Background: Achieving complete response (CR) is a desirable goal in early-to-intermediate-stage hepatocellular carcinoma (HCC). While systemic and locoregional therapies show promise, optimal drug discontinuation criteria remain unclear. This study aims to investigate drug-off criteria for atezolizumab plus bevacizumab as a proof-of-concept study.

Diagnostic performance of attenuation imaging versus controlled attenuation parameter for hepatic steatosis with MRI-based proton density fat fraction as the reference standard: a prospective multicenter study.

Background: Attenuation Imaging (ATI) and controlled attenuation parameter (CAP) are non-invasive ultrasound-based methods for diagnosing hepatic steatosis. However, reports on the clinical usefulness of ATI are limited. We aimed to compare the ability of ATI and CAP to diagnose hepatic steatosis with magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) as the reference standard.

The Current Status of Tumor Markers as Biomarkers in the Era of Immunotherapy for Hepatocellular Carcinoma: Alpha-Fetoprotein Alone Is Not Sufficient.

Introduction: Rapid development of systemic treatments has resulted in improved prognosis for unresectable hepatocellular carcinoma (uHCC) patients. Since immune therapy shows a favorable therapeutic efficacy, use of tumor markers as biomarkers for monitoring treatment response is necessary. This study aimed to elucidate changes in positive rates of 3 available tumor markers in Japan, including alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and lens culinaris agglutinin-reactive AFP (AFP-L3) in uHCC patients treated with systemic therapies over time.

Survival Outcomes Associated With Radiological Progressive Disease Subtypes in Patients With Atezolizumab and Bevacizumab-Treated HCC.

Background And Aim: To assess the relationship between survival outcomes and subtypes of radiological progressive disease (PD) in patients with hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Atezo/Bev).

Methods: A total of 462 patients with Atezo/Bev-treated HCC diagnosed with radiological PD during follow-up were enrolled. PD was classified into three categories: progression or emergence of intrahepatic lesions (PD-IH), macroscopic vascular invasion (PD-MVI), and extrahepatic spread lesions (PD-EHS).

Evaluation of Treatment Outcomes Using dNLR and GNRI in Combination Therapy With Atezolizumab and Bevacizumab for Hepatocellular Carcinoma.

Aim: This study aims to investigate the clinical utility of the derived neutrophil-to-lymphocyte ratio (dNLR) and the Geriatric Nutritional Risk Index (GNRI) in predicting treatment outcomes for patients with unresectable hepatocellular carcinoma (HCC) undergoing combination therapy with atezolizumab and bevacizumab (Atez/Bev).

Methods: A retrospective analysis was conducted on 310 patients. The dNLR, NLR, and GNRI were calculated, and their impact on progression-free survival (PFS) and overall survival (OS) was assessed.

QTL-Based Evidence of Population Genetic Divergence in Male Territorial Aggressiveness of the Japanese Freshwater Threespine Stickleback.

Territorial aggression is widespread across the animal kingdom and is expressed in diverse ecological and social contexts. In addition, there are marked variations in the degree of male reproductive territoriality within and between species. These differences are often attributed to genetic components.